Evidence map›Paper›PMID 27401842›Full record

ArticleGynecologic oncology2016

Novel epigenetic changes in CDKN2A are associated with progression of cervical intraepithelial neoplasia.

N Ari Wijetunga, Thomas J Belbin, Robert D Burk, Kathleen Whitney, Maria Abadi, John M Greally, Mark H Einstein, Nicolas F Schlecht

Open access · greenAbstract read
In one paragraph

Article in Gynecologic oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
3.8field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed, 36 citations in OpenAlex.

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  16. DNA methylation profiles in cancer diagnosis and therapeutics.Clinical and experimental medicine · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 1 institution in 1 country.

N Ari WijetungaDepartment of Genetics and Center for Epigenomics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Thomas J BelbinDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Robert D BurkDepartment of Pediatrics (Genetics), Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Microbiology & Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Kathleen WhitneyDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Maria AbadiDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
John M GreallyDepartment of Genetics and Center for Epigenomics, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Pediatrics (Genetics), Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: john.greally@einstein.yu.edu.
Mark H EinsteinDepartment of Obstetrics & Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: mark.einstein@einstein.yu.edu.
Nicolas F SchlechtDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine (Oncology), Albert Einstein College of Medicine, Bronx, NY 10461, USA. Electronic address: nicolas.schlecht@einstein.yu.edu.
Albert Einstein College of Medicine · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI STEVEN C. ALMO · 1985 to 2026
$111.2M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007288 · NIGMS · YESHIVA UNIVERSITY · PI AKABAS, MYLES H. · 1985 to 2022
$35.6M
NCI NIH HHS P30 CA013330NIGMS NIH HHS T32 GM007288
6 · The paper itself

Abstract

objectiveTo conduct a comprehensive mapping of the genomic DNA methylation in CDKN2A, which codes for the p16(INK4A) and p14(ARF) proteins, and 14 of the most promising DNA methylation marker candidates previously reported to be associated with progression of low-grade cervical intraepithelial neoplasia (CIN1) to cervical cancer.

methodsWe analyzed DNA methylation in 68 HIV-seropositive and negative women with incident CIN1, CIN2, CIN3 and invasive cervical cancer, assaying 120 CpG dinucleotide sites spanning APC, CDH1, CDH13, CDKN2A, CDKN2B, DAPK1, FHIT, GSTP1, HIC1, MGMT, MLH1, RARB, RASSF1, TERT and TIMP3 using the Illumina Infinium array. Validation was performed using high resolution mapping of the target genes with HELP-tagging for 286 CpGs, followed by fine mapping of candidate genes with targeted bisulfite sequencing. We assessed for statistical differences in DNA methylation levels for each CpG loci assayed using univariate and multivariate methods correcting for multiple comparisons.

resultsIn our discovery sample set, we identified dose dependent differences in DNA methylation with grade of disease in CDKN2A, APC, MGMT, MLH1 and HIC1, whereas single CpG locus differences between CIN2/3 and cancer groups were seen for CDH13, DAPK1 and TERT. Only those CpGs in the gene body of CDKN2A showed a monotonic increase in methylation between persistent CIN1, CIN2, CIN3 and cancers.

conclusionOur data suggests a novel link between early cervical disease progression and DNA methylation in a region downstream of the CDKN2A transcription start site that may lead to increased p16(INK4A)/p14(ARF) expression prior to development of malignant disease.

Indexed as

AdultAgedCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18Disease ProgressionDNA MethylationEpigenesis, GeneticFemaleGenes, p16Genes, Tumor SuppressorHumansMiddle AgedOncogene ProteinsUterine Cervical DysplasiaUterine Cervical NeoplasmsYoung AdultCDK2AP2 protein, humanCDKN2A protein, humanCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18Oncogene ProteinsBiomarkerCervical cancerCINMethylationp14p16

Identifiers

PMID27401842
PMCPMC5125392
OpenAlexW2466380713

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.